Abstract: The complex model structure of human immunodeficiency virus-1 (HIV-1) DNA with integrase (IN) dimer (IN2) was refined through molecular dynamics (MD) simulation, and the viral DNAconformational change was explored after binding with IN2. The result showed that the viral DNA could be divided into five regions (i.e. non-binding region, high-affinity region 1, weak-affinity region, high-affinity region 2, and reaction region) according to the binding power with IN2. The partition rationality for viral DNA was confirmed through binding free energy computation. Compared with the viral DNA before binding with IN2, some big conformational changes occurred for the bases in the four binding regions other than the non-binding region for the viral DNA complexed with IN2. The obvious deviation from standard B-DNA in the viral DNA main chain of the complex and the broading of the minor groove in the binding site were both the structural basis for the recognition of viral DNA with IN. The simulation results basically agreed with experimental data, which provided some structural information for the drug design based on the structure of HIV-1 IN.